Innate defense regulator peptide 1018 in wound healing and wound infection

  • Innate defense regulators (IDRs) are synthetic immunomodulatory versions of natural host defense peptides (HDP). IDRs mediate protection against bacterial challenge in the absence of direct antimicrobial activity, representing a novel approach to anti-infective and anti-inflammatory therapy. Previously, we reported that IDR-1018 selectively induced chemokine responses and suppressed pro-inflammatory responses. As there has been an increasing appreciation for the ability of HDPs to modulate complex immune processes, including wound healing, we characterized the wound healing activities of IDR-1018 \(\textit {in vitro}\). Further, we investigated the efficacy of IDR-1018 in diabetic and non-diabetic wound healing models. In all experiments, IDR-1018 was compared to the human HDP LL-37 and HDP-derived wound healing peptide HB-107. IDR-1018 was significantly less cytotoxic \(\textit {in vitro}\) as compared to either LL-37 or HB-107. Furthermore, administration of IDR-1018 resulted in a dose-dependent increase in fibroblast cellular respiration. \(\textit {In vivo}\), IDR-1018 demonstrated significantly accelerated wound healing in \(\textit {S. aureus}\) infected porcine and non-diabetic but not in diabetic murine wounds. However, no significant differences in bacterial colonization were observed. Our investigation demonstrates that in addition to previously reported immunomodulatory activities IDR-1018 promotes wound healing independent of direct antibacterial activity. Interestingly, these effects were not observed in diabetic wounds. It is anticipated that the wound healing activities of IDR-1018 can be attributed to modulation of host immune pathways that are suppressed in diabetic wounds and provide further evidence of the multiple immunomodulatory activities of IDR-1018.

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Metadaten
Author:Lars SteinsträßerGND, Tobias HirschGND, Matthias SchulteGND, Maximilian KückelhausGND, Frank JacobsenGND, Evgenija MerschGND, Ingo StrickerGND, Nicole AfacanGND, Håvard JenssenORCiDGND, Robert E. W. HancockGND, Jason KindrachukGND
URN:urn:nbn:de:hbz:294-72997
DOI:https://doi.org/10.1371/journal.pone.0039373
Parent Title (English):PLoS ONE
Publisher:Public Library of Science
Place of publication:San Francisco
Document Type:Article
Language:English
Date of Publication (online):2020/07/09
Date of first Publication:2012/08/06
Publishing Institution:Ruhr-Universität Bochum, Universitätsbibliothek
Volume:7
Issue:8, Artikel e39373
First Page:e39373-1
Last Page:e39373-7
Institutes/Facilities:Berufsgenossenschaftliches Universitätsklinikum Bergmannsheil, Klinik für Plastische Chirurgie und Schwerbrandverletzte
open_access (DINI-Set):open_access
Licence (English):License LogoCreative Commons - CC BY 4.0 - Attribution 4.0 International